Novel Anti-Hepatitis B Virus Activity of Euphorbia schimperi and Its Quercetin and Kaempferol Derivatives

Mohammad K Parvez; Sarfaraz Ahmed; Mohammed S Al-Dosari; Mazin A S Abdelwahid; Ahmed H Arbab; Adnan J Al-Rehaily; Mai M Al-Oqail

doi:10.1021/acsomega.1c04320

Novel Anti-Hepatitis B Virus Activity of Euphorbia schimperi and Its Quercetin and Kaempferol Derivatives

ACS Omega. 2021 Oct 21;6(43):29100-29110. doi: 10.1021/acsomega.1c04320. eCollection 2021 Nov 2.

Authors

Mohammad K Parvez¹, Sarfaraz Ahmed¹, Mohammed S Al-Dosari¹, Mazin A S Abdelwahid^{2

3}, Ahmed H Arbab^{1

4}, Adnan J Al-Rehaily¹, Mai M Al-Oqail¹

Affiliations

¹ Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
² Department of Pharmaceutical Chemistry, Al-Neelain University, Khartoum 11114, Sudan.
³ Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8576, Japan.
⁴ Department of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan.

Abstract

Natural or plant products, because of their structural diversity, are a potential source for identifying new anti-hepatitis B virus (HBV) agents. Here, we report the anti-HBV activity of Euphorbia schimperi and its quercetin (QRC) and kaempferol derivatives. The anti-HBV-active methanol fraction of E. schimperi was subjected to chromatographic techniques, leading to isolation of three flavonols, following their structure determination by ¹H and ¹³C NMR spectroscopies. Their cytotoxicity and anti-HBV potential were assessed using HBV reporter HepG2.2.15 cells, and their modes of action were delineated by molecular docking. The isolated compounds identified as quercetin-3-O-glucuronide (Q3G), quercetin-3-O-rhamnoside (Q3R), and kaempferol-3-O-glucuronide (K3G) were non-cytotoxic to HepG2.2.15 cells. The viral HBsAg/HBeAg production on day 5 was significantly inhibited by K3G (∼70.2/∼73.4%), Q3G (∼67.8/∼72.1%), and Q3R (∼63.2%/∼68.2%) as compared to QRC (∼70.3/∼74.8%) and lamivudine (∼76.5/∼84.5%) used as standards. The observed in vitro anti-HBV potential was strongly supported by in silico analysis, which suggested their structure-based activity via interfering with viral Pol/RT and core proteins. In conclusion, this is the first report on the anti-HBV activity of E. schimperi-derived quercitrin-3-O-glucuronide, quercitrin-3-O-rhamnoside, and kaempferol-3-O-glucuronide, most likely through interfering with HBV proteins.